Murine mammary tumor viruses (MuMTV's) form a unique and important group of retroviruses, since they are the only viruses known whose main pathologic manifestation is a carcinoma. Investigations of these viruses have been handicapped due to the lack of appropriate in vitro systems to study their biology. Using improved techniques for infecting cultured cells with MuMTV, we shall initiate isolation of mutants that have deletions in their genome. These mutants will be characterized for their biochemical and biological properties. Several approaches will be used to develop in vitro systems to study MuMTV-induced transformation of mouse mammary cells. Although all mouse strains contain MuMTV proviruses, not all strains develop mammary tumors. The low mammary tumor incidence strains control the expression of their MuMTV provirus at the transcriptional and sometimes translational level. The genetic and biochemical basis for these controls and their effects on mammary tumorigenesis will be investigated.